Biosynthesis of sesquiterpenoid

Maier, W., B. Schneider et al. (1998). Biosynthesis of sesquiterpenoid cyclohexenone derivatives in mycorrhizal barley roots proceeds via the glyceraldehyde 3-phosphate/pyruvate pathway. Tetrahedron Lett. 39(7) 521-524. 

An excellent review of the isolation, structural elucidation, total synthesis, and postulated biosynthesis of sesquiterpenoids based on the spiro[4,5]decane (vetis-pirane) skeleton has been published." Further studies on the development of alternative routes to the vetispirane sesquiterpenoids have been described. In one report100 the spirocyclic acetal (217), previously used as an intermediate in the synthesis of (—)-a-acorenol (218),101,102 has been converted into (—)-agarospirol (219) and (-)-/3-vetivone (220) by the reaction sequence outlined in Scheme 26. 

The proposed intermediacy of humulene (218) in the biosynthesis of sesquiterpenoids belonging to various structural groups (caryophyllane, protoilludane, etc.)... 

Scheme 4.1 Biosynthesis of sesquiterpenoid and diterpenoid a-methylene-y-lactones.

The structure of simularene (123), a new structurally interesting sesquiterpenoid isolated from soft coral (Simularia mayi), has been established by A-ray analysis. It has been suggested that the cyclosesquifenchene skeleton of simularene (123) is derived by rearrangement of the intermediate (122) proposed in the biosynthesis of a-and /8-copaene (124). 

Scheme 23. A schematic representation of the postulated involvement of a protoilludane intermediate (213) in the biosynthesis of various sesquiterpenoid...

The mevalonate-independent pathway is present in most bacteria and all phototropic organisms. In higher plants and most algae both pathways run independently. The mevalonate pathway is located in the cytoplasm and is responsible for the biosynthesis of most sesquiterpenoids. The mevalonate-independent pathway, in contrast, is restricted to the chloroplasts where plastid-related isoprenoids such as monoterpenes and diterpenes are biosynthesised via this pathway [43-45]. Figure 4.2 illustrates the interrelationships of both biosynthetic pathways connected to Fig. 4.1 [46]. 

Figure 6.10 De novo biosynthesis of isoprenoid pheromone components by bark and ambrosia beetles through the mevalonate biosynthetic pathway. The end products are hemiterpenoid and monoterpenoid pheromone products common throughout the Scolytidae and Platypodidae (Figure 6.9A). The biosynthesis is regulated by juvenile hormone III (JH III), which is a sesquiterpenoid product of the same pathway. The stereochemistry of JH III is indicated as described in Schooley and Baker (1985). Although insects do not biosynthesize sterols de novo, they do produce a variety of derivatives of isopentenyl diphosphate, geranyl diphosphate, and farnesyl diphosphate. Figure adapted from Seybold and Tittiger (2003).

Perforatone (46) and perforenones A (47 R = OH) and B (47 R = Cl) have been discovered in the marine alga Laurencia perforata.78 It is suggested that (46) and (47) are formed from a chamigrene cation (48), and this hypothesis provides a full rationale for the biosynthesis of the wide variety of sesquiterpenoids that have been isolated from Laurencia species. 

The pentalane class of sesquiterpenoids has received substantial attention in the past year from the standpoints of structural elucidation, biosynthesis, and synthesis. Two new metabolites of this class are pentalenic acid (298) and pentalenolactone H (299). Both these compounds have a secondary hydroxyl function adjacent to the gem-dimethyl group and are thus potential precursors of pentalenolactone (300) in which one of these methyl groups has undergone a 1,2-migration. Cane and Rossi " have now identified a further metabolite of a Streptomyces strain which has been named pentalenolactone E (301) and is now... 

Figure 1 Schematic overview of the biosynthesis of the monoterpenoids, sesquiterpenoids, diterpenoids, and triterpenoids. Representatives of these classes with biological relevance are shown. Enzymatic steps are indicated in italics DMADP, dimethylallyl diphosphate CDP, geranyl diphosphate GGDP, geranylgeranyl diphosphate FDP, farnesyl diphosphate IDP, isopentenyl diphosphate.

This chapter follows the pattern of previous Reports with the various sesquiterpenoids considered in structural groups based on their postulated or established biosynthesis. Interest in sesquiterpenoid structure, synthesis, and biosynthesis has continued at a high level during the period covered by the present Report. Two excellent reviews have been published one provides an up-to-date account of sesquiterpenoid biosynthesis while the other provides an authoritative description of studies on sesquiterpenoid stress compounds. Stress metabolites are produced by plants after infection with fungi, bacteria, and viruses or after mechanical wounding, irradiation with u.v. light, dehydration, cold, or treatment with phytotoxic agents. 

The predicted involvement of brominated monocyclofarnesane derivatives in the biosynthesis of halogenated chamigrane sesquiterpenoids cf. Vol. 4, p. 96 Vol. 5, p. 55 Vol. 6, p. 64) has received considerable support by the recent isolation of a - (13) and /S-snyderol (14) from species of marine red alga (Laurencia obtusa and L. 

Epoxytrichothec-9-ene (138) (cf. Vol, 4, p. 90), a metabolite of T. roseum and a proposed intermediate in the biosynthesis of trichothecene sesquiterpenoids cf. Chapter 6), has recently been synthesized (Scheme 16). The final cyclization step [(136) (137)] in the synthesis is identical to that proposed in the biosynthesis... 

A protoilludane intermediate (225) (c/. Vol. 4, p. 113) has been implicated in the biosynthesis of protoilludane, illudane, illudalane, and marasmane sesquiterpenoids... 

The suggested intermediacy of hirsutene (239) in the biosynthesis of the hirsutane sesquiterpenoids has been supported by its recent isolation from Coriolus consors. In addition an alternative synthesis of this compound has been accomplished by the route outlined in Scheme 26. 

A complete account of the experimental evidence leading to the structural elucidation of the first members (244a—d) of the capnellane group of sesquiterpenoids has been provided in a recent paper cf. Vol. 5, p. 70). These compounds (244a—d) are found in soft coral (Capnella imbricata) and it has been suggested that their biosynthesis involves cyclization of humulene followed by methyl migration from C-5 to C-4 [cf. (245)]. 

A new synthetic approach to the synthesis of germacrane sesquiterpenoids involving cyclization of 10,ll-epoxy-rran5,trans-farnesyl phenyl sulphide (306) provides a mixture of hedycaryol (307) and the isomeric alcohols (308) and (309). Studies on the biosynthesis of germacrane sesquiterpenoids have appeared recently. 

Reports are available on the discovery of insect anti-feeding substances and anti-juvenile hormones, on the homology of biosynthetic routes and its basis in chemotaxonomy, and on the role of terpenoids in chemical ecology. Further speculations have been made about the biosynthesis of various classes of sesquiterpenoid based on the results of a study of the quantitative co-occurrence of these in the genus Hymenaea. 

New drimane sesquiterpenoids include 6p-acetoxyisodrimenin (74), capsico-dendrin, a partially characterized tetramer of cinnamodial (63),45 albicanyl 3,4-dihydroxycinnamate (75), albicanyl 2,4-dihydroxycinnamate (76) (both liverwort constituents),48 and polyveoline (77), an indolosesquiterpenoid.47 Full details of the isolation and structural determination of pebrolide (78) and its congeners (79) and (80) have been published.48 The biosynthesis of pebrolide... 

Terpenoids are widespread natural products that are formed from C5 isoprene units leading to their characteristic branched chain structure. Terpenoids are divided into families on the basis of the number of isoprene units from which they are formed. Thus there are monoterpenoids (Cio), sesquiterpenoids (C15) diterpenoids (C20), sesterterpenoids (C25), triterpenoids (C30) and carotenoids (C40). The isoprene units are normally linked together in a head-to-tail manner. However, the C30 triterpenoids and C40 carotenoids are formed by the dimerization of two Ci5 and C20 units, respectively. Hence, in these cases the central isoprene units are linked in a head-to-head manner. The presence of tertiary centres in the isoprenoid backbone of the terpenoids facilitates skeletal rearrangements in the biosynthesis of these natural products. As a consequence, on first inspection some structures appear not to obey the isoprene rule. 

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